Spyre Therapeutics Inc美股招股说明书(2026-04-16版)

PROSPECTUS SUPPLEMENT(To Prospectus dated February 27, 2026) Common Stock We are offering 6,500,000 shares of our common stock, par value $0.0001 per share (“common stock”). The public offering price foreach share of common stock is $62.00. Our common stock is traded on the Nasdaq Global Select Market under the symbol “SYRE.” On April 14, 2026, the last reported saleprice per share of our common stock was $64.01. Public offering priceUnderwriting discounts and commissionsProceeds to Company before expenses(1) (1)See “Underwriting” beginning on pageS-18of this prospectus supplement for additional information regarding underwriting compensation. We have granted the underwriters an option to purchase up to an additional 975,000shares of our common stock from us, at the publicoffering price, less underwriting discounts and commissions, within 30 days of the date of this prospectus supplement. Investing in our securities involves a high degree of risk. You should carefully consider the risks and uncertainties describedunder the heading “Risk Factors” on pageS-7of this prospectus supplement and in the accompanying prospectus, as well asthose contained in the other documents that are incorporated by reference. You should carefully read this entire prospectussupplement and the accompanying prospectus, including any information incorporated by reference, before deciding whetherto purchase shares of our common stock. Neither the U.S. Securities and Exchange Commission nor any state securities commission has approved or disapproved ofthese securities or passed upon the adequacy or accuracy of this prospectus supplement or the accompanying prospectus. Anyrepresentation to the contrary is a criminal offense. The underwriters expect to deliver the shares of common stock on or aboutApril 16, 2026. Joint Book-Running Managers Passive BookrunnerLifeSci Capital April 14, 2026 TABLE OF CONTENTS Prospectus Supplement ABOUT THIS PROSPECTUS SUPPLEMENTCAUTIONARY NOTE CONCERNING FORWARD-LOOKING STATEMENTSPROSPECTUS SUPPLEMENT SUMMARYTHE OFFERINGRISK FACTORSUSE OF PROCEEDSCAPITALIZATIONDILUTIONCERTAIN MATERIAL U.S. FEDERAL INCOME TAX CONSIDERATIONSUNDERWRITINGEXPERTSLEGAL MATTERSWHERE YOU CAN FIND MORE INFORMATIONINCORPORATION OF CERTAIN INFORMATION BY REFERENCE Prospectus ABOUT THIS PROSPECTUSCAUTIONARY STATEMENT CONCERNING FORWARD-LOOKING STATEMENTSTHE COMPANYRISK FACTORSUSE OF PROCEEDSSECURITIES WE MAY OFFERDESCRIPTION OF SECURITIESPLAN OF DISTRIBUTIONLEGAL MATTERSEXPERTSWHERE YOU CAN FIND MORE INFORMATIONINCORPORATION OF CERTAIN INFORMATION BY REFERENCE ABOUT THIS PROSPECTUS SUPPLEMENT This prospectus supplement and the accompanying prospectus form part of a registration statement on Form S-3 (File No. 333-293600) that we filed with the U.S. Securities and Exchange Commission (the “SEC”) on February 19, 2026, utilizing a “shelf”registration process, and which became effective on February 27, 2026. Under this shelf registration process, we may, from time totime, sell common stock and other securities, including in this offering. This document contains two parts. The first part consists ofthis prospectus supplement, which provides you with specific information about this offering. The second part consists of theaccompanying prospectus, which provides more general information, some of which may not apply to this offering. Generally, whenwe refer only to the “prospectus,” we are referring to both parts combined. This prospectus supplement may add, update or changeinformation contained in the accompanying prospectus. To the extent that any statement we make in this prospectus supplement isinconsistent with statements made in the accompanying prospectus, or any documents incorporated by reference, the statements madein this prospectus supplement will be deemed to modify or supersede those made in the accompanying prospectus, including thedocuments incorporated by reference therein. Information in any document we subsequently file that is incorporated by reference shallmodify or supersede the information in this prospectus supplement, the accompanying prospectus and documents incorporated byreference prior to such subsequent filing. It is important for you to read and consider all information contained in this prospectussupplement and the accompanying prospectus, including the documents we have referred you to in the section entitled “Where YouCan Find More Information” below in this prospectus supplement. We are responsible for the information contained and incorporated by reference in this prospectus supplement and theaccompanying prospectus. We have not authorized anyone to give you any other information, and we take no responsibility for anyother information that others may give you. We are not making offers to sell the securities in any jurisdiction in which an offer orsolicitation is not authorized or permitted or in which the person making such offer or solicitation is not qualified to do so or to anyoneto w